Various studies have demonstrated that the topography of cell environment leads to significant cell modulations. Hence, the aim of this work was a systematic approach to investigate the ability of several synthetic microstructures on a cell-friendly base polymer to control neuronal cell development regarding morphology and differentiation. This approach should provide basic knowledge for cell culture substrates that deliver healthy cells in high numbers, easy culturing and defined cell development to neuronal target tissue. Neural and bone cells were grown on PMMA microscopy slides with several surface structures, including cubes or walls at the low micrometer scale. To produce the surface structures, mold inserts comprising the microstructure negative were confected by LIGA lithographic process. Final PMMA slide fabrication was established by variotherm injection molding. For efficient and effective handling in the cell laboratory, a special assembly was designed. Microstructure analysis was carried out by SEM, AFM and contact angle measurements. Cell behaviour was determined using LSM for morphology and RT-PCR for gene expression analysis. SEM and AFM proved that the demolding quality was appropriate. Gene expression analysis of the cells on microstructures indicated no influence on cell differentiation compared to non-structured control. However, a profound impact on cell morphology, especially an elongation alongside walls, and on cell adhesion, especially on cubes, was shown with LSM. Further, contact angle measurements with water and diiodomethane on microstructures denoted enhanced hydrophobic traits on cubes that counteracted the focal adhesion of cells and pronounced surface energy anisotropy on walls that caused a lengthwise spreading of the test liquid droplet, similar to cell elongation. The latter could be caused in both cases by asymmetrical energy barrier heights. Hence, we propose a water-drop-model that might deliver a common physicochemical cause regarding the similar cell and droplet geometries on microstructures and non-structured control. Furthermore, the water-drop-model might shed light on the lack of cell adhesion on cubes.